I tie with embroidery floss and use a small or medium curved needle.
I start in the middle of the quilt and then every 4", after that's done, then I offset my ruler 2" vertical and horizontal and then tie again every 4". Most the quilts I've seen that are tied are probably tied every 6"-10", that probably depends on the batting, but regardless if I'm using poly or cotton, I still do it every 4", I like the looks of it better.
I've never had a problem with my knots coming loose.